Prenatal and early postnatal food restrictions cause changes in brain oxidative status and orexigenic/anorexigenic hormones in the offspring of rats: prevention by quercetin and kaempferol

Abstract

Brain oxidative signaling pathways have been identified as important targets for alleviating food deprivation-induced changes in metabolic gate-ways. Previous studies have shown that prenatal and early postnatal malnutrition alters leptin and ghrelin signaling via oxidative pathways. Thus, it has been hypothesized that agents with antioxidant properties might be beneficial for the mitigation of prenatal and early postnatal food scarcity-induced oxidative damage. Quercetin and kaempferol are natural bioflavonoids with proven antioxidant properties. In this study, we evaluated their effects on prenatal maternal food consumption, maternal and pup weights, biomarkers of orexigenic and anorexigenic hormones and oxidative stress in rats. Rats were allotted into different treatment groups (n ​= ​6) in three different experiments (prenatal, postnatal food-deprivations or both). Prenatal-food restriction (PrNFR) was induced by 50% of ad libitum accessible diet during pregnancy till parturition and postnatal-food restriction (PsNFR) was simulated by litter-enlargement to 16 pups per mother from postnatal day (PND) 2. Rats in each experiment were concurrently treated with vehicle (10 ​mL/kg), quercetin (50, 100 and 200 ​mg/kg, p.o.) or kaempferol (50, 100 and 200 ​mg/kg, p.o.) respectively. A third experimental group consisted of both protocols. Quercetin and kaempferol dose-dependently increased the body weights of pups exposed to PrNFR, PsNFR and PrNFR-PsNFR at PNDs 1–22 respectively. Both compounds increased maternal body weights but attenuated maternal food-intake at prenatal days 7 and 14 due by PrNFR. Quercetin and kaempferol reduced brain malondialdehyde concentrations and increased glutathione levels in PrNFR, PsNFR and PrNFR-PsNFR-exposed offspring of rats. Importantly, quercetin and kaempferol significantly (p ​< ​0.05) prevented PrNFR-, PsNFR- or PrNFR-PsNFR-induced alterations in leptin and ghrelin levels. Cumulatively, quercetin and kaempferol increased pup and maternal weights and attenuated maternal food-intake of rats submitted to PrNFR, PsNFR and PrNFR-PsNFR respectively, likely via nutrigenomic modulations of orexigenic/anorexigenic hormones and inhibition of brain oxidative stress.